Abstract
Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation. Here, we show that TSC1-2 is required for insulin signaling to PI3K. TSC1-2 maintains insulin signaling to PI3K by restraining the activity of S6K, which when activated inactivates insulin receptor substrate (IRS) function, via repression of IRS-1 gene expression and via direct phosphorylation of IRS-1. Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors.
Original language | English |
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Pages (from-to) | 213-223 |
Number of pages | 11 |
Journal | Journal of Cell Biology |
Volume | 166 |
Issue number | 2 |
DOIs | |
Publication status | Published - 19 Jul 2004 |
Keywords
- 6K
- Nsulin
- PI3K
- RS proteins
- TSC1-2
ASJC Scopus subject areas
- Cell Biology